The D1 dopamine receptor, localized in the striatum, is a potential target for anti-Parkinsonian agonist drugs and for cocaine medications. Although brain entry and stimulation of D1 receptors by D1 agonists is inferred by behavioral effects, brain imaging is an effective method for relating receptor occupancy to behavioral response. We investigated the occupancy of D1 receptors by a high efficacy D1 agonist SKF 81297, a drug shown to improve motor function in a monkey model of Parkinson's disease (MPTP model). Three cynomolgus monkeys (Macaca fascicularis) were injected with [11C] SCH 39166 to label D1 dopamine receptors. Baseline values for D1 receptor levels (striatum:cerebellum ratios) were 1.77 q 0.10, 1.86 q 0.09, 2.07 q 0.18 at 40, 60 and 90 min after injection, resp. In a second set of experiments, 20 min after radioisotope, SKF 81297 was administered at a dose (1 mg/kg) that does not affect spontaneous motor function in control animals. Under these conditions, occupancy of the D1 receptor by the agonist was not detectable. A parallel experiment conducted in an MPTP-treated monkey showed a significant level of D1 receptor binding by the D1 agonist. These preliminary data suggest that occupancy of the D1 receptor by agonists may be higher under conditions in which dopamine neurons are depleted of